NEPHROPROTECTIVE ACTIVITY OF PLUMERIA RUBRA AGAINST CISPLATIN INDUCED NEPHROTOXICITY IN EXPERIMENTAL RATS
Keywords:Plumeria rubra, Cisplatin, Nephrotoxicity, Creatinine, Oxidative stress
Objective: The current study was designed to evaluate the protective effect of standardized hydroalcoholic extract of Plumeria rubra (HAEPR) against cisplatin-induced nephrotoxicity in Wistar rats.
Methods: HAEPR was administered orally at 3 dose levels (100,200,400 mg/kg). Vitamin E (250 mg/kg) was used as a Standard nephroprotective agent. The kidney function test (estimation of serum creatinine, albumin, blood urea nitrogen) oxidative stress study (estimation of superoxide dismutase, malondialdehyde activity) and histological examination of kidneys was conducted.
Results: The efficacy of HAEPR was compared with Cisplatin (CP) treated group. Serum creatinine and BUN was significantly (p<0.01) elevated in CP-treated group compared to the control group. HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) decreased the serum creatinine and BUN levels. CP treated group exhibited significant (p<0.01) decrease in albumin when compared to control. Significant (p<0.01) increase in the serum albumin level was found in HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) compared to CP group. Significant (p<0.01) decrease in the activity of SOD was observed in the CP group as compared to control. HAEPR (100 and 200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) increased SOD levels. HAEPR (400 mg/kg) significantly (p<0.05) increased SOD levels. HAEPR (100,200,400 mg/kg) significantly (p<0.01) decreased MDA levels as compared to CP group. Histopathological examination of the kidneys showed that HAEPR markedly ameliorated Cisplatin-induced renal tubular necrosis. An extract was found effective at all doses, although low dose (100 mg/kg) was found to be more effective and comparable with the standard group (Vitamin E 250 mg/kg).
Conclusion: Present investigation revealed that HAEPR resulted in attenuation of Cisplatin-induced renal damage in rats.
Kirstin Hendrickson, Why is the Urinary System Important? Livestrong.com. Available from: http://www.livestrong.com/article/200414-why-is-the-urinary-system-important. [Last accessed on 28 Nov 2018]
Kidney Disease. labtestsonline.org. Available from: https://labtestsonline.org/understanding/conditions/kidney/start. [Last accessed on 20 Oct 2018]
Sahu BD, Kalvala AK, Koneru M, Jerald MK, Kuncha MS, Rachamalla SS, et al. Ameliorative effect of fisetin on cisplatin induced nephrotoxicity in rats via modulation of NF-kB activation and antioxidant defence. Plos One 2014;9:1-15.
Kuhlmann MK, Burkhardt G, Kohler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant 1997;12:2478-80.
Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol 2003;23:460-4.
Chatterjee P, Mukherjee A, Nandy S. Protective effects of the aqueous leaf extract of aloe barbadensis on gentamicin and cisplatin-induced nephrotoxic rats. Asian Pac J Trop Biomed 2012;2:S1754-S1763.
Hayati F, Hossainzadeh M, Shayanpour S, Gheshlaghi ZA, Mousavi SS. Prevention of cisplatin nephrotoxicity. J Nephropharmacol 2016;5:57-60.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins 2010;2:2490-518.
Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. Am J Med Sci 2007;334:115-4.
Sibi G, Awasthi S, Dhananjaya K, Mallesha H, Ravikumar KR. Comparative studies of Plumeria species for their phytochemical and antifungal properties against citrus sinensis pathogens. Int J Agric Res 2012;7:324-31.
Rasool SN, Jaheerunnisa S, Chitta SK, Jayaveera KN. Antimicrobial activities of Plumeria acutifolia. J Med Plants Res 2008;2:77-80.
Ramalingam R, Sivakumar T. In-vitro and in-vivo anticancer activity of leaves of plumeria alba Linn. J Pharm Res 2009; 2:203-7.
Radha R, Kavimani S, Ravichandran V. Antitumour activity of methanolic extract of plumeria alba L. leaves against dalton lymphoma ascites in mice. Int J Health Res 2008;1:79-85.
Rekha JB, Jayakar B. Anticancer activity of ethanolic extract of leaves of plumeria rubra L. Curr Pharm Res 2011;1:175.
Yadav AV, Undale VR. Antidiabetic activity of plumeria rubra L. in normal and alloxan-induced diabetic mice. Int J Basic Clin Pharmacol 2016;5:884-9.
Yadav AV, Undale VR. Antidiabetic effect of plumeria rubra L. in streptozotocin-induced diabetic rats. Int J Pharm Sci Res 2017;8:1806-12.
Merina AJ, Sivanesan D, Begum VH, Sulochana N. Antioxidant and hypolipidemic effect of Plumeria rubra L. in alloxan induced hyperglycemic rats. J Chem 2010;7:1-5.
Yousef MI, Saad AA, El Shennawy LK. Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 2009;47:1176-83.
Debnath S, Babre N, Manjunath YS, Mallareddy V, Parameshwar P, Hariprasath K. Nephroprotective evaluation of ethanolic extract of the seeds of papaya and pumpkin fruit in cisplatin-induced nephrotoxicity. J Pharm Sci Tech 2010;2:241-6.
Yadav AV, Upasani CD. Nephroprotective activity of asparagus racemosus against cisplatin-induced nephrotoxicity and renal dysfunction in experimental rats. Asian J Pharm Clin Res 2018;11:230-3.
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302.
Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-74.
Rajagopal G, Toora BD. Practical biochemistry. 2nd edition. Ahuja publishing house; 2005. p. 98-112.
Fawcett JK, Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol 1960;13:156-9.
Bancroft D, Stevens A, Turner R. Theory and practice of histological technique. 4th edition. Churchill Livingstone, Edinburgh, London, Melbourne; 1996. p. 53-83.
Ilic S, Stojiljkovic N, Veljkovic M, Veljkovic S, Stojanovic G. Protective effect of quercetin on cisplatin-induced nephrotoxicity in rats. Facta Universitatis, Series: Med Biol 2014;16:71-5.
Viswanathan V, Snehalatha C, Kumutha R, Jayaraman M, Ramachandran A. Serum albumin levels in different stages of type 2 diabetic nephropathy patients. Indian J Nephrol 2004;14:89-92.
Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst 2008;9:189-95.
Domitrovic R, Potocnjak I, Orlic ZC, Skoda. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food Chem Toxicol 2014;66:321-8.
Gautam RK, Singh RK, MS Karchuli. Evaluation of nephroprotective activity of mentha arvensis in cisplatin-induced nephrotoxicity. Asian J Pharm Clin Res 2014;7:188-91.
Gupta SK, Najnin I, Choudhuri C, Mandal P. Elicitation of therapeutic potential and oxidative stress assessment of fenugreek sprouts under UV irradiation. Int J Pharm Pharm Sci 2017;9:91-9.